DEE WILSON CONSULTING
Book Review:
Impactful read on the history of medicine
So Very Small: How Humans Discovered the Microcosmos, Defeated Germs and May Still Lose the War Against Infectious Disease
Thomas Levenson, 2025
I cannot speak too highly of Thomas Levenson's new book. This is one of the best books about the history of medicine I've ever read, and it has a fascinating story to tell about both the struggle to understand, prevent and treat infectious diseases such as puerperal fever, smallpox, cholera, hospital gangrene, anthrax and tuberculosis and also the obstacles to scientific progress, including strong opposition from many scientists and physicians who tenaciously resisted various applications of germ theory for more than a hundred years.
It is difficult for modern humans who are not historians to fully appreciate the toll in lives and suffering resulting from infectious diseases prior to the mid- twentieth century. Levenson states that "In 1850, ... infections caused almost half of all deaths in England and Wales. ... In the United States, the top killers for 1900 were pneumonia, influenza, tuberculosis and gut infections, which together accounted for half the American lives lost that year. Now? In the developed world infectious diseases barely register as a cause of death, even during a pandemic." Prior to the modern era, pandemics of a few infectious diseases such as smallpox and cholera devastated entire societies and spread around the world, killing millions of people, while causing unimaginable suffering.
According to Levenson, there were five cholera pandemics during the nineteenth century. Cholera often killed its victims quickly and with excruciating pain. Regarding cholera victims, Levenson states: "Pain would build in their stomachs -- and always the diarrhea would persist and worsen. That's when the archetypal mark of cholera showed itself ... As Bell wrote: they were 'like water in which grain has been boiled with pieces ... of opaque white or yellowish coagulated matter floating in it.' After several sudden total and often violent defecations, 'the disease moved fast. The eyes would sink into the dying patients' sockets. Their faces would shrink in on themselves, contorting into agonized expressions unrecognizable to their most intimate friend. They could suffer agonizing spasms, or report burning sensations even as their skin became cold. The shit and vomit would continue to flow, extracting the last fluid that could possibly be extracted ..." Most cruelly: the sufferer was "in most cases coherent to the last." All this happened at a breakneck pace. The usual time from first symptom to death was sixteen hours ..."
Smallpox was an especially lethal killer. Levenson states: " In the late eighteenth century, smallpox still killed about 400,000 Europeans a year and blinded one third of survivors ..." In colonial America "there were six outbreaks from 1633-1698." For most of human history, infectious diseases killed far more soldiers than died in battle or from wounds inflicted by weapons of war. Levenson asserts that a minimum estimate of deaths of soldiers in the U.S. Civil War is 620,000, and I have read estimates of 750,000- 800,000 total deaths. Levinson asserts: "... while 200,000 men died in combat or from wounds suffered on the battlefield, most of the lives lost from Ft. Sumter to Appomattox - at least 400,000 -- were taken ... by disease and infection." Levenson estimates that, during W.W. I, one sixth of 9-11 million deaths of soldiers on both sides were due to infectious diseases.
One of the best parts of So Very Small is the story of the lengthy effort to understand the cause of and prevent hospital gangrene which often occurred when, in the aftermath of surgery, an injury that was healing normally began to swell. A Scottish surgeon, John Bell, wrote: "The sore inflames, then comes vomiting, diarrhea and a distinct fever, and the disease seizes plainly on the wounded part." Soon, exposed tissue "is melted down into a fetid mucus." As the infection progresses, "the pain is dreadful, the cries of the suffering are the same in the night as in the day-time..." Furthermore, one case on a ward could lead to an epidemic that could travel between floors accompanied by "a most pungent and intolerable fetor."
Before germ theory was widely accepted, physicians attempting to prevent or treat hospital gangrene worked by trial and error, Levenson states. Middleton Goldsmith, a Union surgeon during the Civil War, pioneered the use of bromine, a halogen, to disinfect wounds. He and his colleagues developed an effective though gruesome solution: "cut away as much of the diseased flesh as possible, scrape way any oozing fluid, using a scalpel, cut out any pulpy matter attached to the skin. Then inject a solution of bromine and water onto the exposed tissue and into every cavity in the wound." Sometimes, in deep wounds, bromine had to be injected (using a pointed stick of wood) into the "gangrenous material" itself. Chloroform was used in only the worst cases when a patient was unusually intolerant of pain. Extreme peril justified extreme measures, Levenson states. This procedure cured gangrene but did not help to cope with other infectious diseases. Finding an effective solution for a specific horrific condition was not the same as having a powerful theory with multiple applications.
The Discovery of Microbes and the Delayed Development of Germ Theory
In So Very Small, Levenson repeatedly returns to the question of why there was a two hundred year delay between the discovery of microbes by Antoine van Leeuwenhoek in 1676 and the widespread validation and acceptance of germ theory in the late 19th century. Levenson states: "One reason was that older ideas about how disease worked -- that it was the result of conditions of decay, bad air, squalor, or simply sin - remained plausible for a very long time." These explanations had elements of truth, e.g. "wretched living conditions are connected to poor health" and "appeared to explain what was observed." However, Levenson maintains, the availability of alternative explanations does not fully account for the stubborn resistance to new evidence, or the vilification of proponents of innovative ideas and practices based on natural experiments such as comparing outcomes for patients with similar conditions treated in dissimilar ways.
One source of resistance was the reluctance of physicians to admit that they had been spreading infectious disease through unhygienic practices, such as failure to thoroughly clean and disinfect their hands, surgical instruments, etc. before and after treating patients in hospital settings. Ignaz Semmelweis, the physician who figured out the cause of puerperal fever in women who had recently given birth by analyzing conditions in two distinct wards of a Vienna hospital, suffered "professional exile, dismissal, madness, death, dishonor and oblivion" after "admission of his own and his colleagues" failure." He was beaten to death in an insane asylum where he had been placed by family members due to his unhinged behavior. The idea that physicians had been responsible for many thousands of deaths of women following childbirth (more than one in ten mothers in one ward of the hospital where Semmelweis was employed during the 1840s) was an intolerable idea to many of his peers.
John Snow, an English physician, developed detailed maps of cholera outbreaks in London in 1848-49 and in 1854 showing the relationship between the spread of the disease and neighborhoods' use of different sources of water. London's medical establishment "resolutely" opposed Snow's analysis. "The General Board of Health .. produced four reports and a scientific appendix totaling 660 pages in which its authors explored correlations between cholera cases and the weather-- air and water temperature, humidity, rainfall, the amount of ozone, and much more." The Board concluded that "cholera fermented out of either air or water when conditions were grotesque enough to brew up the poison."
This was not merely an academic argument among scholars and physicians; public health was at stake. Snow's insistence that contaminated water was the cause of cholera was ignored. In 1866, a new cholera outbreak in London killed 4,000 people. London constructed a new water system in the 1870 after which cholera disappeared, Levenson states.
One reason that proponents of germ theory were ignored for so long is that they were often unknowns, without easy access to publishing their findings in highly regarded journals, and so were unable to generate interest in their ideas, or were not medical professionals. One of the earliest proponents in the U.S. of using tiny amounts of smallpox as a vaccine against full blown infection was Cotton Mather, the fire and brimstone Protestant divine. Robert Koch, the German physician who discovered the cause of anthrax, was not a part of university or major teaching hospital when he began his efforts to understand the pathogen responsible for anthrax, a disease that killed 90% of those persons who contracted it and farm animals as well. Koch had to struggle for recognition and to prevent better known scientists from taking credit for his breakthroughs. In Levenson's account of momentous discoveries, many physicians and scientists come off badly, both for their refusal to fairly consider evidence re causes of infections and possible cures and for using character assassination to silence lower status opponents. Furthermore, the logic of scientific explanation was being developed by investigators. Scientific method in medicine was rudimentary at best for many years prior to the late 19th century.
Koch was one of the first physicians to employ germ theory in his investigation of causes of a disease. Before germ theory, investigators in battlefields and hospitals with unusually high percentages of deaths from a specific disease were searching for solutions, an effective response to the challenges they faced in saving their patients' lives. They were not theorists of infectious diseases, a concept that took two hundred years to develop. However, once germ theory was accepted as the path to treating infectious diseases, everything changed. Levenson states: "Germ theory was essential to what came next -- a series of victories over one malady after another, over infections born of war, accident or contagion. ...Taken together, these discoveries became a Promethean gift, as momentous as the discovery of fire."
-- Dee Wilson